General procedure for the synthesis of 8-bromo-2-methylquinoline-2-carboxylic acid using 8-bromo-2-methylquinoline as starting material: selenium dioxide (100 g, 0.9 mol) was dissolved in dioxane (1 L), heated to reflux and 8-bromo-2-methylquinoline (35.2 g, 0.16 mol) was added all at once. The reaction mixture was stirred under reflux conditions for 3 h followed by thermal filtration. The filtrate was concentrated and purified by silica gel column chromatography (eluent: pure dichloromethane) to afford the aldehyde intermediate as a light yellow solid (39 g, 100% yield). Subsequently, a solution of NaClO2 (108 g, 1.19 mol) and NaH2PO4 (108 g, 0.9 mol) in water (1 L) was slowly added to the above mixture of aldehyde (27 g, 0.11 mol), BuOH (700 mL) and 2-methylbut-2-ene (150 mL) over 30 min. The reaction mixture was stirred at room temperature overnight. After completion of the reaction, the mixture was concentrated, diluted by adding water (500 mL), the precipitate was collected by filtration and dried to give 8-bromoquinoline-2-carboxylic acid as a brown solid (25 g, 90% yield). Results of mass spectrometry analysis: calculated value C10H6BrNO2: 250.96; measured value: 252 [M+1].
